Metachromatic leukodystrophy (MLD) is an autosomal recessive inherited disorder of sulfatide metabolism. The disease affects adults as well as children. In children MLD (late infantile and juvenile form) is diagnosed with relative ease because of prominent early neurologic involvement and pervasive neuropathological changes. However, the adult form the disease may be more of a challenge in clinical recognition because it may masquerade as a psychiatric illness over a prolonged period without dramatic neurologic involvement. The adult variety has been variously diagnosed as schizophrenia, manic depressive illness, alcoholism and dementia. The main objective of this research project is to begin to place the disorder in the proper perspective in regard to prevalence by determining the presence of the typical biochemical abnormalities indicative of MLD in a cohort of chronic psychiatric patients. The metabolic basis of MLD is a generalized and profound deficiency of Arylsulfatase A (ASA; sulfatidase, sulfatide degrading enzyme). Specifically, we plan to determine; 1) the activity of Arylsulfatase A in urine and leukocytes, and 2) the excretion of sulfatides in urine, in two hundred chronic hospitalized psychiatric patients and fifty normal adults. The activity of ASA in leukocytes will be assayed using both nitrocatechol sulfate and sulfatide (natural) as substrates.